14 CLINICAL STUDIES
14.1 Skeletal Muscle Relaxation for Intubation of Adult Patients
The efficacy of Cisatracurium Besylate Injection to provide skeletal muscle relaxation to facilitate tracheal intubation during surgery was established in six studies in adult patients. In all these studies patients had general anesthesia and mechanical ventilation.
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- Cisatracurium Besylate Injection doses between 0.15 and 0.2 mg/kg were evaluated in 240 adults. Maximum neuromuscular blockade generally occurred in within 4 minutes for this dose range.
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- When administered during induction using thiopental or propofol and co-induction agents (i.e., fentanyl and midazolam), excellent to good intubating conditions were generally achieved within 2 minutes (excellent intubation conditions most frequently achieved with the 0.2 mg/kg dose of Cisatracurium Besylate Injection).
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- Following the induction of general anesthesia with propofol, nitrous oxide/oxygen, and co-induction agents (e.g., fentanyl and midazolam), good or excellent conditions for tracheal intubation occurred in 96/102 (94%) patients in 1.5 to 2 minutes following cisatracurium doses of 0.15 mg/kg and in 97/110 (88%) patients in 1.5 minutes following cisatracurium doses of 0.2 mg/kg.
In Study 1, the clinically effective duration of action for 0.15 and 0.2 mg/kg Cisatracurium Besylate Injection using propofol anesthesia was 55 minutes (range: 44 to 74 minutes) and 61 minutes (range: 41 to 81 minutes), respectively.
In Studies 2 and 3, Cisatracurium Besylate Injection doses of 0.25 and 0.4 mg/kg were evaluated in 30 patients under opioid/nitrous oxide/oxygen anesthesia and provided 78 (66–86) and 91 (59–107) minutes of clinical relaxation, respectively.
In Study 4, two minutes after fentanyl and midazolam were administered, patients received thiopental anesthesia. Intubating conditions were assessed at 120 seconds following administration of 0.15 mg/kg or 0.2 mg/kg of Cisatracurium Besylate Injection in 51 patients (see Table 11).
| Cisatracurium Besylate 0.15 mg/kg (n = 26) | Cisatracurium Besylate 0.20 mg/kg (n = 25) | |
|---|---|---|
| *Excellent: Easy passage of tube without coughing. Vocal cords relaxed and abducted. Good: Passage of tube with slight coughing and/or bucking. Vocal cords relaxed and abducted. | ||
Excellent and Good | 88% | 96% |
95% CI | 76,100 | 88,100 |
Excellent | 31% | 60% |
Good | 58% | 36% |
Excellent intubating conditions were more frequently achieved with the 0.2 mg/kg dose (60%) than the 0.15 mg/kg dose (31%) when intubation was attempted 120 seconds following cisatracurium.
Study 5 evaluated intubating conditions after 3 and 4 × ED95 (0.15 mg/kg and 0.20 mg/kg) following induction with fentanyl and midazolam and either thiopental or propofol anesthesia. This study compared intubation conditions produced by these doses of cisatracurium after 90 seconds. Table 12 displays these results.
| Intubating Conditions | Cisatracurium Besylate 0.15 mg/kg with Propofol (n = 31) | Cisatracurium Besylate 0.15 mg/kg with Thiopental (n = 31) | Cisatracurium Besylate 0.20 mg/kg with Propofol (n = 30) | Cisatracurium Besylate 0.20 mg/kg with Thiopental (n = 28) |
|---|---|---|---|---|
| * Excellent: Easy passage of tube without coughing. Vocal cords relaxed and abducted. Good: Passage of tube with slight coughing and/or bucking. Vocal cords relaxed and abducted. | ||||
Excellent and Good | 94% | 90% | 93% | 96% |
95% CI | 85,100 | 80,100 | 84,100 | 90,100 |
Excellent | 58% | 55% | 70% | 57% |
Good | 35% | 35% | 20% | 39% |
Excellent intubating conditions were more frequently observed with the 0.2 mg/kg dose when intubation was attempted 90 seconds following cisatracurium.
14.2 Skeletal Muscle Relaxation for Intubation of Pediatric Patients
The efficacy of Cisatracurium Besylate Injection to provide skeletal muscle relaxation to facilitate tracheal intubation was established in studies in pediatric patients aged 1 month to 12 years old. In these studies, patients had general anesthesia and mechanical ventilation.
In Study 6, a Cisatracurium Besylate Injection dose of 0.1 mg/kg was evaluated in 16 pediatric patients (ages 2 years to 12 years) during opioid anesthesia. When administered during stable opioid/nitrous oxide/oxygen anesthesia, maximum neuromuscular blockade was achieved in an average of 2.8 minutes (range: 1.8 to 6.7 minutes) with a clinically effective block for 28 minutes (range: 21 to 38 minutes).
In Study 7, a Cisatracurium Besylate Injection dose of 0.15 mg/kg was evaluated in 50 pediatric patients (ages 1 month to 12 years) during opioid anesthesia. When administered during stable opioid/nitrous oxide/oxygen anesthesia, maximum neuromuscular blockade was achieved in an average of about 3 minutes (range: 1.5 to 8 minutes) with a clinically effective block for 36 minutes (range: 29 to 46 minutes) in 24 patients ages 2 to 12 years. In 27 infants (1 to 23 months), maximum neuromuscular block was achieved in about 2 minutes (range: 1.3 to 4.3 minutes) with a clinically effective block for about 43 minutes (range: 34 to 58 minutes) with this dose.
Study 7 also evaluated intubating conditions in 180 pediatric patients (ages 1 month to 12 years) after administration of Cisatracurium Besylate Injection doses of 0.15 mg/kg following induction with either halothane (with halothane/nitrous oxide/oxygen maintenance) or thiopentone and fentanyl (with thiopentone/fentanyl nitrous oxide/oxygen maintenance). Table 13 displays the intubating conditions by type of anesthesia, and pediatric age group. Excellent or good intubating conditions were produced 120 seconds following 0.15 mg/kg of cisatracurium besylate in 88/90 (98%) of patients induced with halothane and in 85/90 (94%) of patients induced with thiopentone and fentanyl. There were no patients for whom intubation was not possible, but there were 7/120 patients aged 1 year to 12 years old for whom intubating conditions were described as poor.
| Cisatracurium Besylate 0.15 mg/kg 1–11 mo. | Cisatracurium Besylate 0.15 mg/kg 1–4 years | Cisatracurium Besylate 0.15 mg/kg 5–12 years | ||||
|---|---|---|---|---|---|---|
| Halothane Anesthesia (n=30) | Thiopentone/Fentanyl Anesthesia (n=30) | Halothane Anesthesia (n=30) | Thiopentone/Fentanyl Anesthesia (n=30) | Halothane Anesthesia (n=30) | Thiopentone/Fentanyl Anesthesia (n=30) | |
| * Excellent: Easy passage of the tube without coughing. Vocal cords relaxed and abducted. Good: Passage of tube with slight coughing and/or bucking. Vocal cords relaxed and abducted. Poor: Passage of tube with moderate coughing and/or bucking. Vocal cords moderately adducted. Response of patient requires adjustment of ventilation pressure and/or rate. | ||||||
Excellent and Good | 100% | 100% | 97% | 87% | 97% | 97% |
Excellent | 100% | 83% | 90% | 63% | 73% | 70% |
Good | 0% | 17% | 7% | 23% | 23% | 27% |
Poor | 0% | 0% | 3% | 13% | 3% | 3% |
14.3 Skeletal Muscle Relaxation in ICU Patients
Long-term infusion (up to 6 days) of cisatracurium besylate during mechanical ventilation in the ICU was evaluated in two studies.
Study 8 was a randomized, double-blind study using presence of a single twitch during train-of-four (TOF) monitoring to regulate dosage. Patients treated with cisatracurium besylate (n = 19) recovered neuromuscular function (T4:T1 ratio ≥ 70%) following termination of infusion in approximately 55 minutes (range: 20 to 270).
In Study 9, cisatracurium besylate patients recovered neuromuscular function in approximately 50 minutes (range: 20 to 175; n = 34).